Guided Intracellular Delivery using Precise Area Introduction and Transfection (PAINT)

PROJECT SUMMARY The objective of the proposed project is to develop a method called PAINT (Precise Area INtroduction and Transfection) for highly localized, versatile, and efficient biomolecule delivery for “direct-write” guided administration at spatial resolutions from single cell to hundreds of cells. One

current approach that is commonly used to deliver biomolecules to cells involves viral or non-viral transfection. These methods do not offer the ability to target delivery of cargo to a subset of cells. Furthermore, they are limited in which cargoes they can deliver efficiently. In contrast, physical

delivery methods offer control over the spatial distribution of cellular modification and are compatible with a wider range of cargo, but currently operation is too difficult, and versatility is too limited for them to gain widespread use. The proposed effort addresses these limitations with a new technology called PAINT, which will enable very precise control over the spatial distribution

of cellular modification, i.e., introduction of nucleic acids (RNA, DNA), proteins, nanoparticles or viruses, using a novel combination of physical delivery means to transiently disrupt the cell membrane thus enabling cargo entry at a rate orders of magnitude greater than the current state of the art. The proposed new technology will be embodied in a PAINT “brush,” a stylus that

delivers from one set of nozzles a cold plasma, and from a very closely located adjacent set (